The long-term aims of this project are 1) to establish the genetic control points governing assembly of the retina, a complex but relatively accessible part of the central nervous system, and 2) to provide new ideas that may lead to the prevention and treatment of inherited human diseases of the retinitis pigmentosa group. The essential feature of these diseases is a progressive degeneration of retinal photoreceptor cells. The project concentrates on describing and analyzing several new inherited diseases causing a similar loss of retinal photoreceptor cells in the mouse, the most favorable mammalian species, along with man, for analyzing genetic disorders. In the forthcoming three years, we propose to present the initial description of diseases caused by three independent mouse genes, named wabbler lethal-2J (wl2J), vitiligo (vit), and hugger (hug). The wabbler lethal disorder may be present in two forms caused by independent mutations, wl and wl2J, both at the wabbler lethal locus, but this will be clear only when the wl mice are bred so as to eliminate a complicating disease that prevents expression of the putative wl retinal disorder. The plan of study involves development of comparable, uniform genetic stocks so that the diseases can be compared quantitatively and reliably with one another and with previously described mouse diseases that are somewhat like human retinitis pigmentosa, but not identical. The vit and hug genes will be mapped, wl having already been mapped to a position about one-third of the distance from the centromere to the far end of chromosome 14. The timing of the photoreceptor cell loss will be measured from microscope specimens, and the cause of the cell loss will be sought by immunocytochemical and tissue grafting methods. The most promising clue at present is that all three diseases involve defects in length and integrity of rod outer segments, the part of the photoreceptor cell that contains the light-absorbing pigment. Mechanisms controlling rod outer segment growth and structure will be sought, in the hope of intervening to slow the pace of the disease. Mice will be made available to other investigators upon request.